title: Combination studies of platinum(II)-based metallointercalators with buthionine-S,R-sulfoximine, 3-bromopyruvate, cisplatin or carboplatin.
abstract: With current chemotherapeutic treatment regimes often limited by adverse side effects, the synergistic combination of complexes with anticancer activity appears to offer a promising strategy for effective cancer treatment. This work investigates the anti-proliferative activity using a combination therapy approach where metallointercalators of the type [Pt(IL)(AL)](2+) (where IL is the intercalating ligand and AL is the ancillary ligand) are used in combination with currently approved anticancer drugs cisplatin and carboplatin and organic molecules buthionine-S,R-sulfoximine and 3-bromopyruvate. Synergistic relationships were observed, indicating a potential to decrease dose-dependent toxicity and improve therapeutic efficacy.
authors.affiliation: Nanoscale Organisation and Dynamics Group, School of Science and Health, University of Western Sydney, Locked Bag, 1797, Penrith South DC, 2751, NSW, Australia. j.aldrich-wright@uws.edu.au.
authors.forename: K Benjamin
authors.initials: KB
authors.lastname: Garbutcheon-Singh
authors.forename: Benjamin W J
authors.initials: BW
authors.lastname: Harper
authors.forename: Simon
authors.initials: S
authors.lastname: Myers
authors.forename: Janice R
authors.initials: JR
authors.lastname: Aldrich-Wright
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000627:therapeutic use; D019328:Buthionine Sulfoximine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D016190:Carboplatin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010984:Platinum / Q000737:chemistry; D011773:Pyruvates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011773:Pyruvates; D010984:Platinum; D019328:Buthionine Sulfoximine; C017092:bromopyruvate; D016190:Carboplatin; D005978:Glutathione; D002945:Cisplatin